Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment

Simple Summary The gut microbiome has been shown to play a role in carcinogenesis and the progression of cancer, in part through its interaction with the host immune system. Research from numerous clinical cohorts and preclinical models suggests that gut microbes contribute to response and toxicity to cancer treatment-including chemotherapy, immunotherapy, and radiation. Furthermore, disrupting the gut microbiome with broad spectrum antibiotics negatively impacts the outcomes to cancer therapy. Studies have shown improved oncologic outcomes to immunotherapy and other treatment in the setting of specific dietary patterns, such as a high fiber diet. Accordingly, therapeutic strategies including fecal microbiome transplant, pre/probiotics, and dietary interventions have emerged aiming to improve patient outcomes and are being tested in ongoing clinical trials. The aim of the present work is to provide an update on the available evidence regarding how gut microbes and other factors affect the response and toxicity to cancer therapy, with opportunities to target these therapeutically. The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can be modulated through strategies, such as fecal transplant. We also summarize the current literature that implicate high fiber and ketogenic diets in improved response rates to immunotherapy and chemotherapy, respectively. Finally, we discuss the relevance of these findings in the context of patient care, advocate for a holistic approach to cancer treatment, and comment on the next frontier of targeted gut and tumor microbiome modulation through novel therapeutics, dietary intervention, and precision-medicine approaches.